It is estimated that about 50 million people in the United States suffer from persistent, serious pain. Response to pain involves both peripheral and central mechanisms with several systems, neurotransmitters and receptors playing a role in pain transmission and response. The neural structures supporting the perception of pain as experience of an unpleasant stimulus strongly overlap with those that support the experience of negative emotion and those areas proposed to be involved in a final common pathway for initiation of drug seeking behaviors in addiction. How acute pain in response to an injury or disease transitions to a chronic pain syndrome, and the underlying neurobiology of pain are still poorly understood. This project proposes to extend previous findings using functional Magnetic Resonance Spectroscopy (fMRS) in pain by linking changes in neural activation to changes in concentration of the neurotransmitter glutamate and one of it's intermediates, glutamine, in response to pain. We hypothesize 1) that painful stimuli administered to healthy humans will increase central neuronal activity and glutamatergic neurotransmission in regions of the brain associated with pain perception, 2) Glutamine levels measured with 1H-MRS will reflect relative levels of activity and glutamatergic transmission and 3) Pain thresholds will be negatively correlated with reports of negative emotion and somatic complaints, while glutamate and glutamine responses to a painful stimulus will be positively correlated with these same measures. The ability to measure such activation and neurotransmitter increases will provide a novel surrogate marker for categorizing pain syndromes. Such investigations of the underlying central neurochemical responses to pain and the development of a technique to precisely measure these responses will have implications extending beyond a better understanding of pain and improving pain treatment and may even impact on the important related issue of addiction to analgesics. [unreadable] [unreadable] [unreadable]